Ultrasonography: Original Research
Serial Third-Trimester Ultrasonography
Compared With Routine Care in
Uncomplicated Pregnancies
A Randomized Controlled Trial
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Olaide Ashimi Balogun, MD, Baha M. Sibai, MD, Claudia Pedroza,
Tyisha L. Barrett, and Suneet P. Chauhan, MD, HonDSc
OBJECTIVE: To evaluate whether serial ultrasound ex-
aminations in the third trimester increase identification
of a composite of growth or amniotic fluid abnormalities
when compared with routine care among pregnancies
that are uncomplicated between 24 0/7 and 30 6/7 weeks
of gestation.
METHODS: Women without complications between 24
0/7 and 30 6/7 weeks of gestation were randomized
(NCT0270299) to either routine care (control arm) or
ultrasound examination every 4 weeks (intervention
arm). The primary outcome was a composite of abnor-
malities of fluid volume and growth: oligohydramnios or
polyhydramnios; fetal growth restriction; or large for
gestational age. The secondary outcome was the pres-
ence of composite maternal or neonatal morbidity
among the two groups. A total of 206 participants was
From the Department of Obstetrics, Gynecology, and Reproductive Sciences,
McGovern Medical School, and the Center for Clinical Research and Evidence-
Based Medicine, Department of Pediatrics, University of Texas Health Science
Center at Houston, Houston, Texas.
Supported in part by the Larry C. Gilstrap MD Center for Perinatal and
Women’s Health Research.
Presented at the 37th annual meeting of the Society for Maternal-Fetal Medicine,
January 29–February 3, 2018, Dallas, Texas.
Each author has indicated that he or she has met the journal’s requirements for
authorship.
Received June 7, 2018. Received in revised form August 10, 2018. Accepted
August 23, 2018. Peer review history is available at http://links.lww.com/AOG/
B189.
Corresponding author: Olaide Ashimi Balogun, MD, Department of Obstetrics,
Gynecology, and Reproductive Sciences, University of Texas Health Science
Center at Houston, 6431 Fannin Street, MSB 3.270 Houston, TX 77030;
email: Olaide.A.Ashimi@uth.tmc.edu.
Financial Disclosure
The authors did not report any potential conflicts of interest.
© 2018 by the American College of Obstetricians and Gynecologists. Published
by Wolters Kluwer Health, Inc. All rights reserved.
ISSN: 0029-7844/18
1358 VOL. 132, NO. 6, DECEMBER 2018
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PhD, Sean C. Blackwell, MD,
needed to have 80% power to detect an increase in the
primary composite outcome from 10% in control to 25%
in the intervention group (baseline rate 10%; two-tailed;
a50.05; loss to follow-up 5%). All women were included
in the intent-to-treat analysis. Fisher exact, x2 tests, or
two-sample t tests were used to assess group differences.
RESULTS: From July 11, 2016, to May 24, 2017, 852
women were screened for eligibility and 206 were
randomized as follows: 102 in routine care and 104 in
serial ultrasound examinations. The two groups were
comparable in baseline characteristics. The primary com-
posite outcome was significantly higher among women
who were in the ultrasound examination group than the
routine care group (27% vs 8%; relative risk 3.43, 95% CI
1.64–7.17); five women (95% CI 3–11) were needed to
identify at least one of the composite ultrasound abnor-
malities. Although we were underpowered to detect a sig-
nificant difference, the following secondary endpoints
occurred with similar frequency in the ultrasound exami-
nation group than the routine care group: induction re-
sulting from abnormal ultrasound examination findings
(14% vs 6%), cesarean delivery in labor (5% vs 6%), and
prespecified composite maternal morbidity (9% in both
groups) and composite neonatal morbidity (1% vs 4%).
CONCLUSION: Among uncomplicated pregnancies
between 24 0/7 and 30 6/7 weeks of gestation, serial
third-trimester ultrasound examinations were signifi-
cantly more likely to identify abnormalities of fetal
growth or amniotic fluid than measurements of fundal
height and indicated ultrasound examination. No differ-
ences in maternal and neonatal outcomes were noted,
although we were underpowered for these endpoints.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
NCT02702999.
(Obstet Gynecol 2018;132:1358–67)
DOI: 10.1097/AOG.0000000000002970
OBSTETRICS & GYNECOLOGY
C urrently, the American College of Obstetricians
and Gynecologists (ACOG) recommends that
the first step in screening for abnormalities of fetal
growth or amniotic fluid volume in uncomplicated
pregnancies is serial measurements of fundal height,
starting at 24 weeks of gestation. If a discrepancy
between gestational age and measurement of the fun-
dus is present, the second step is to obtain an ultra-
sound examination to assess fetal weight and amniotic
fluid volume.1,2 As a result of routine care, a substan-
tial portion of small for gestational age (birth weight
less than the 10th percentile for gestational age) or
large for gestational age (LGA; birth weight greater
than the 90th percentile for gestational age) and oli-
gohydramnios or polyhydramnios is unidentified3–6
and therefore may not benefit from antepartum sur-
veillance and interventions.7–9
Abnormal growth occurs in 16% of uncompli-
cated pregnancies.10 These pregnancies are more
likely to result in stillbirths or have neonates with
morbidities.11–13 Abnormalities of amniotic fluid vol-
ume—oligohydramnios or polyhydramnios—occur in
up to 10% of low-risk pregnancies and are associated
with stillbirth, low Apgar score, and neonatal mortal-
ity.6,14–17 There is an impetus to improve the identi-
fication of fetal growth restriction (estimated fetal
weight less than the 10th percentile for gestational
age), ultrasonographic LGA (estimated fetal weight
greater than the 90th percentile for gestational age),
oligohydramnios, and polyhydramnios.
The purpose of this randomized clinical trial was
to compare the identification of composite of abnor-
malities of fluid volume and growth—oligohydram-
nios, polyhydramnios, fetal growth restriction, or
ultrasonographic LGA—in uncomplicated pregnancies
by performing serial fundal height measurements and
ultrasound examination if there was a discrepancy
compared with serial ultrasound examination every
4 weeks, regardless of the measurement of fundal
height. We focused on this composite because after
a normal second-trimester anatomy ultrasound exam-
ination, these are the most common abnormalities
identified6 and because the purpose of fundal height
measurements is to screen for these four abnormal
conditions.
MATERIALS AND METHODS
This single-centered randomized controlled trial com-
menced after obtaining approval from institutional
review board at The McGovern Medical School–
University of Texas at Houston and registering on
ClinicalTrials.gov (NCT0270299). Inclusion criteria
were women who were at least 18 years old, had
VOL. 132, NO. 6, DECEMBER 2018 Ashimi Balogun et al
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a singleton pregnancy with no major prenatally
diagnosed fetal anomalies, and who had an estimated
due date based on in vitro fertilization or ultrasound
examination before 22 0/7 weeks.18 Women were
excluded for any medical complication or co-
morbidity at the time of randomization (Box 1). If
a complication developed after randomization,
women remained in the group to which they were
randomized.
Trained research staff approached eligible women
and obtained informed, written consent between 24
Box 1. Exclusion Criteria
First ultrasound examination after 22 wk of gestation
Women with any of the following comorbidities:
a. Autoimmune disorders (antiphospholipid anti-
body, systemic lupus erythematous, rheuma-
toid arthritis, scleroderma)
b. Cerclage in the index pregnancy
c. Diabetes mellitus—gestational or pregestational
d. Hematologic disorders (coagulation defects,
sickle cell disease, thrombocytopenia, and
known thrombophilia)
e. Hypertension (chronic or gestational hyperten-
sion, or preeclampsia with or without severe
features before enrollment)
f. Human immunodeficiency virus
g. Prior obstetric history of 1) small for gesta-
tional age; 2) preterm birth before 34 wk of
gestation; 3) severe preeclampsia, eclampsia,
hemolysis, elevated liver enzymes, and low
platelet count syndrome; and 4) stillbirth after
24 wk of gestation or neonatal death
h. Preterm labor or ruptured membranes before
enrollment
i. Psychiatric disorder (bipolar, depression) on
medication
j. Placenta previa or 3rd-trimester bleeding
k. Renal insufficiency (serum creatinine greater
than 1.5 mg/dL)
l. Chronic lung disease (asthma requiring medi-
cation, chronic obstructive pulmonary disease)
m. Fetal red blood cell isoimmunization
n. Seizure disorder on medication
o. Thyroid disease on medication
p. Body mass index greater than 40 kg/m2 at first
prenatal visit
Major fetal anomaly including:
a. Anencephaly
b. Spina bifida
c. Bilateral renal agenesis
d. Cystic hygroma with hydrops
e. Diaphragmatic hernia
f. Congenital heart defects
Women who were unable to sign a consent in the
English language
Institutionalized individuals (prisoners)
Third-Trimester Ultrasonography vs Routine Care 1359
0/7 to 30 6/7 weeks of gestation after it was
determined they did not have gestational diabetes.19
Enrolled participants were randomly assigned in
a one-to-one ratio using permuted block randomiza-
tion to prevent imbalances between groups. The ran-
dom allocation sequence was developed in R software
by the statistician (C.P.) who was not involved in the
conduct of the study. The randomization table was
uploaded to REDCap. Treatment allocation was as-
signed through the randomization module. Partici-
pants were assigned to either routine care, which
included serial fundal height measurements at each
clinical appointment prompting an ultrasound exam-
ination if a discrepancy was present (routine arm), or
ultrasound examination every 4 weeks (at approxi-
mately 30, 34, and 38 weeks of gestation), regardless
of fundal height measurements (intervention arm).
Women enrolled, ultrasonographers, and maternal–
fetal medicine attendings reviewing the ultrasound
examinations and the chart abstractor were not blin-
ded to the group allocation.
Clinicians treating these women were informed of
the ultrasound findings if any of the following were
noted: fetal growth restriction, LGA, oligohydram-
nios, polyhydramnios, or any ultrasound findings that
would influence clinical treatment (eg, spontaneous
bradycardia or previously undetected fetal anomaly).
Women with abnormal findings were notified. The
clinicians treated their patients according to ACOG
guidelines.1,7,8 In both groups, additional ultrasound
examinations could be obtained if deemed necessary
by the obstetric care provider if complications devel-
oped (eg, preterm labor, decreased fetal movements,
or development of hypertensive disease). Registered
diagnostic medical ultrasonographers did all the ultra-
sound examinations and a maternal–fetal medicine
subspecialist reviewed all ultrasound examinations.
Obstetrics–gynecology faculty and residents training
under their supervision did all of the fundal height
measurements. To reflect daily clinical practice,
standardization of measurements of biometric parts,
amniotic fluid, or fundal height was not done for this
trial.
The fetal weight was estimated by obtaining
measurements of the biparietal diameter, head cir-
cumference, abdominal circumference, and femoral
diaphysis length. The regression equation proposed
by Hadlock et al20 was used to estimate the fetal
weight. Fetal growth abnormalities were defined if
the estimated fetal weight was less than the 10th per-
centile or greater than the 90th percentile for gesta-
tional age.1,21,22 Amniotic fluid was assessed using
either the amniotic fluid index or maximum vertical
1360 Ashimi Balogun et al Third-Trimester Ultrasonography vs Routine Care
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pocket. Oligohydramnios was defined as amniotic
fluid index 5.0 cm or less or maximum vertical
pocket 2.0 cm or less. Polyhydramnios was defined
as an amniotic fluid index 24.0 or greater or maxi-
mum vertical pocket 8.0 cm or greater.2 All ultra-
sound reports were made available to the treating
health care providers. Decision-making regarding
the management of each pregnancy was at the discre-
tion of the individual clinician. The nomogram pub-
lished by Alexander et al23 was used to categorize
newborns as small for gestational age (birth weight
less than the 10th percentile for gestational age) or
as actual LGA (birth weight greater than the 90th
percentile for gestational age).
Women recruited to the study were followed
through delivery and information about the remain-
der of their antepartum care; intrapartum and neo-
natal outcomes were abstracted. To keep abstracted
data consistent, one author (O.A.B.) reviewed all the
charts and was aware of the group allocation. Com-
posite maternal morbidity for this trial was defined as
any of the following: 1) chorioamnionitis, 2) cesarean
delivery in labor, 3) wound infection, 4) transfusion, 5)
deep venous thrombus or pulmonary embolism, 6)
admission to the intensive care unit, or 7) death.
Composite neonatal morbidity was defined as any of
the following: 1) Apgar score less than 5 at 5 minutes,
2) umbilical arterial pH less than 7.00, 3) intraven-
tricular hemorrhage grade III or IV, 4) periventricular
leukomalacia, 5) intubation for longer than 24 hours,
6) necrotizing enterocolitis grade 2 or 3, 7) stillbirth
after randomization, or 8) neonatal death (within 28
days) of birth in the index pregnancy.
With routine care, among uncomplicated preg-
nancies, the identification of the composite of abnor-
malities of fluid volume and growth abnormalities is
10%.6 To increase the detection of the composite of
abnormalities of fluid volume and growth abnormal-
ities from 10% in the control arm to 25% in the inter-
vention arm, a total of 194 women needed to be
randomized (a55%; power580%). We estimated that
5% of women would be lost to follow-up based on
a previous pilot study.6 Thus, the total sample size
for the trial was 206 women.
Descriptive statistics were used to summarize all
study variables. Categorical variables were reported
as frequencies and percentages. Fisher exact, x2 tests,
or two-sample t tests were used to assess group differ-
ences (routine vs serial ultrasound examinations) in
patient outcomes. Subgroup analysis was performed
using similar methods. Relative risk (RR) and 95% CI
were calculated as was number needed to identify
the primary composite outcome. All analyses were
OBSTETRICS & GYNECOLOGY
conducted using Stata 13.0. All randomized women
were included in the intent-to-treat analysis.
RESULTS
Recruitment began July 11, 2016, and concluded May
24, 2017. Of the 852 women screened for eligibility,
626 patients did not meet inclusion criteria. The most
common reason for exclusion was women with
comorbidities such as pregestational or gestational
diabetes or chronic hypertension. Two hundred
twenty-six women were approached to participate in
the study and 20 declined. The remaining 206 women
were consented and 102 were randomized to receive
routine care and 104 to receive serial ultrasound
examinations (Fig. 1). One woman in the routine care
group delivered at an outside hospital and the out-
comes of delivery were unavailable for analysis.
The two groups were comparable in baseline
characteristics (Table 1). Women recruited in the trial
were ethnically diverse, approximately 4 in 10 were
nulliparous, and approximately 70% had body mass
indexes (calculated as weight (kg)/[height (m)]2) less
than 30 at the first prenatal visit. The total number of
ultrasound examinations was higher in the interven-
tion arm than the control arm. The indications for the
ultrasound examinations differed as did the gesta-
tional age at delivery (P,.01; Table 2). The total num-
ber of antepartum complications after randomization
was similar in the two groups with approximately one
in four low-risk women developing a complication in
Figure 1. Flow diagram. *Comorbidity
such as hypertension or diabetes.
Ashimi Balogun. Third-Trimester Ultraso-
nography vs Routine Care. Obstet Gynecol
2018.
VOL. 132, NO. 6, DECEMBER 2018 Ashimi Balogun et al
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their third trimester of pregnancy. The most common
antepartum complication was gestational hyperten-
sion or preeclampsia (Table 3).
The primary composite outcome was more fre-
quently identified among women who had serial
ultrasound examinations than those who received
routine care (27% vs 8%; RR 3.4, 95% CI 1.6–7.2).
The number needed to treat was five women (95% CI
3–11). Although the study was not powered to detect
differences in the individual components of the com-
posite outcome, there was a difference in identifica-
tion of polyhydramnios between the serial ultrasound
examination and routine care groups (11% vs 2%; RR
5.4, 95% CI 1.2–23.7). No significant difference in the
detection of fetal growth restriction, LGA, or oligohy-
dramnios was noted (Table 4).
Analysis limited to women who did not develop
any complications after randomization (eg, preterm
labor or hypertensive disease) also indicated the
primary composite outcome was significantly more
frequent among women who had serial ultrasound
examinations than routine care (27% vs 8%; RR 3.7,
95% CI 1.5–9.4). The detection of polyhydramnios
differed between the two groups but the 95% CI was
wide as a result of the sample size (Table 5). The
number needed to treat was also five women (95%
CI 3–13).
Prespecified composite maternal morbidity was
similar in both groups (9% in both serial ultrasound
Third-Trimester Ultrasonography vs Routine Care 1361
Table 1. Characteristics of Participants at Randomization

Characteristic Routine Care (n5102) Serial 3rd-Trimester USE (n5104)

Maternal age (y)

18–19 5 (5) 10 (10)
35 or older 10 (10) 12 (12)
Race–ethnicity
Black 32 (31) 34 (33)
White 23 (23) 25 (24)
Hispanic 20 (20) 22 (21)
Other 27 (27) 23 (22)
Nulliparity 43 (42) 39 (38)
Insurance
Medicaid 66 (65) 69 (66)
Private 36 (36) 35 (34)
BMI at 1st prenatal visit (kg/m2)*
Less than 30 74 (73) 77 (74)
30.0–39.9 28 (27) 27 (26)
1st ultrasound examination (wk) 12.964.3 12.964.3
Gestational age at randomization (wk) 29.261.0 29.061.1
USE, ultrasound examination; BMI, body mass index.
Data are n (%) or mean6SD.
* Women with BMIs of 40 or higher were excluded.

examinations compared with routine care group; RR
1.0, 95% CI 0.4–2.3), but we were not powered to
detect a difference. There were no episodes of deep
venous thrombus or pulmonary embolism, admission
to the intensive care unit, or maternal deaths in either
groups. The prespecified composite neonatal morbid-
ity was also similar in both groups (1% in the serial
ultrasound examination group vs 4% in the routine
care group; RR 0.2, 95% CI 0.03–2.1), but we were
underpowered to detect a difference (Table 6).
The gestational age epoch (less than 32 0/7, 32 0/
7–34 6/7, 35 0/7–36 6/7, or at least 37 0/7 weeks of
gestation) when the abnormal condition was initially
identified differed between the groups (P5.02). The
rate of having a biophysical profile or umbilical artery
Doppler, because of the abnormality noted on

Table 2. Ultrasound Examinations—Indications and Gestational Age

Routine Care (n5101) Serial 3rd-Trimester USE (n5104) P/RR (95% CI)

USE for fetal growth 58 279 4.6 (3.5–6.1)

USE per protocol 0 (0) 264 (2.54) —
No. of women who received additional USE 39 10 .2 (0.1–0.5)
Indications for additional USE
Bleeding 1 (0.026) 0 (0) —
Decreased fetal movement 1 (0.026) 3 (0.3) 11.7 (1.2–112.5)
GA and FH disparity 43 (1.1) 6 (0.6) .5 (0.2–1.3)
HTN disease of pregnancy* 4 (0.10) 1 (0.1) 1.0 (0.1–8.7)
Preterm labor 0 (0) 0 (0) —
PROM 0 (0) 0 (0) —
Others† 9 (0.23) 7 (0.7) 3.0 (1.1–8.1)
GA when USE was done (wk)
Less than 32 0/7 3 (5) 93 (33) ,.01
32 0/7–34 6/7 23 (40) 95 (34)
35 0/7–36 6/7 19 (33) 19 (7)
37 0/7 or greater 13 (22) 72 (26)
USE, ultrasound examination; RR, relative risk; GA, gestational age; FH, fundal height; HTN, hypertensive; PROM, premature rupture of
membranes.
Data are n (number of USE per woman) for USE per protocol and additional USE per indications and n (%) for GA when USE was done.
* Includes gestational hypertension and preeclampsia with or without severe features.
†
Includes cholestasis, fall, fetal ventricular tachycardia.

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Table 3. Antepartum Complications After Randomization

Routine Care (n5102) Serial 3rd-Trimester USE (n5104) RR (95% CI)

Antepartum complications—total* 32 (31) 29 (28) 0.9 (0.6–1.4)

GHTN or preeclampsia 15 (15) 21 (20) 1.4 (0.8–2.5)
Decreased fetal movement 4 (4) 3 (3) 0.7 (0.2–3.2)
Preterm labor 5 (5) 3 (3) 0.6 (0.1–2.4)
PROM at less than 37 wk of gestation 1 (1) 3 (3) 2.9 (0.3–27.8)
Others† 9 (9) 2 (2) 0.2 (0.05–0.98)
USE, ultrasound examination; RR, relative risk; GHTN, gestational hypertension; PROM, premature rupture of membranes.
Data are n (%) unless otherwise specified.
* Defined as admission for at least 24 hours for one of the antepartum complications.
†
Others includes cholestasis, pyelonephritis, fall, fetal ventricular tachycardia.

ultrasound examination (ie, polyhydramnios or intra-
uterine growth restriction), was similar between the
two groups (Table 7).
Gestational age at delivery was comparable in the
two groups with only 9% of women delivering before
37 weeks of gestation in both groups. The most
common reason for induction of labor before 37
weeks of gestation was preeclampsia with severe
features. There was no difference in delivery route
between the two groups (RR 0.8, 95% CI 0.5–1.2).
The most common reason for cesarean delivery in
both groups was for women who declined a trial of
labor and desired a repeat cesarean delivery (Table 8).
DISCUSSION
Our randomized trial suggests that among women
with uncomplicated pregnancies at 24 0/7 to 30 6/7
weeks of gestation, serial third-trimester ultrasound
examinations are more likely to identify a composite
of abnormalities of fetal growth or amniotic fluid than
routine care. The number of women who need serial
ultrasound examinations in the third trimester to
identify an abnormal condition is five (95% CI
3–11). Although the trial is underpowered for assess-
ment of peripartum outcomes, the maternal and
neonatal adverse outcomes were similar as were ges-
tational age at delivery, the rate of induction, and of
cesarean delivery.
Estimates indicate that upward of two thirds of
pregnancies are low risk.6,24,25 Although there are
multiple potential etiologies of adverse outcomes in
low-risk pregnancies, the most common ones that
are amenable to interventions are aberrations of fetal
growth or of amniotic fluid.6,10–17 Small-for-
gestational-age and LGA newborns are significantly
more likely to be stillborn and have neonatal morbid-
ities.1,11,21 Furthermore, pregnancies complicated
with oligohydramnios or polyhydramnios are associ-
ated with stillbirth, low Apgar score, and neonatal
mortality.14–17 Therefore, even among uncomplicated
pregnancies, identification of abnormalities in fetal
growth or in amniotic fluid is central to antepartum
care because the combination of surveillance and in-
terventions could mitigate adverse outcomes.1,7,8,21
Our randomized trial differs from others on the
topic26–30 vis-à-vis the enrollment criteria, the fre-
quency of the ultrasound examinations in the inter-
vention group, and the primary outcome being
a composite of abnormalities of growth or amniotic
fluid. Prior randomized trials on ultrasound examina-
tion after 24 weeks of gestation focused on either
growth restriction26,28–30 or placental grading,27

Table 4. Primary Outcome

Routine Care (n5102) Serial 3rd-Trimester USE (n5104) RR (95% CI)

Primary composite outcome* 8 (8) 28 (27) 3.4 (1.6–7.2)

FGR 2 (2) 8 (8) 3.9 (0.9–18.0)
Ultrasonographic LGA 2 (2) 8 (8) 3.9 (0.9–18.0)
Oligohydramnios 2 (2) 4 (4) 1.9 (0.4–10.5)
Polyhydramnios 2 (2) 11 (11) 5.4 (1.2–23.7)
USE, ultrasound examination; RR, relative risk; FGR, fetal growth restriction (estimated fetal weight less than the 10th percentile for
gestational age—during any ultrasound examination); LGA, large for gestational age (estimated fetal weight greater than the 90th
percentile for gestational age—during any ultrasound examination).
Data are n (%) unless otherwise specified.
* The trial was not powered to detect a difference in the four components of the primary composite outcome.

VOL. 132, NO. 6, DECEMBER 2018 Ashimi Balogun et al Third-Trimester Ultrasonography vs Routine Care 1363

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Table 5. Primary Outcome Without Antepartum Complications

Routine Care Serial 3rd-Trimester USE

(n5102) (n5104) RR (95% CI)

Women without antepartum complication after 70 (69) 75 (72) 1.1 (0.9–1.3)

randomization
Women with primary outcome without antepartum 5 (7) 20 (27) 3.7 (1.5–9.4)
complications
FGR 1 (1) 5 (7) 4.7 (0.6–39.0)
Ultrasonographic LGA 1 (1) 6 (8) 5.6 (0.7–45.4)
Oligohydramnios 2 (2) 2 (3) 0.9 (0.1–6.4)
Polyhydramnios 1 (1) 9 (12) 8.4 (1.1–64.6)
USE, ultrasound examination; RR, relative risk; FGR, fetal growth restriction (estimated fetal weight less than the 10th percentile for
gestational age—during any ultrasound examination); LGA, large for gestational age (estimated fetal weight greater than the 90th
percentile for gestational age—during any ultrasound examination).
Data are n (%) unless otherwise specified.

whereas we focused on a composite of abnormal con-
ditions and did not assess placental grade. With
hypertensive disease of pregnancy, the fetus is primar-
ily at risk for growth restriction and oligohydramnios,
whereas in diabetes, the risks are primarily those of
macrosomia and polyhydramnios.26,28–30 Among
uncomplicated pregnancies, however, it is uncertain
which aspect of abnormality in growth or amniotic
fluid predominates. It is also noteworthy to mention
that most of the prior randomized trials on the topic
were done in the 1980s to 1990s26–28 or
abroad26,27,29,30 and do not reflect contemporary
practice in the United States.
The limitations of this randomized trial should be
acknowledged. The likelihood of identifying individ-
ual component of the composite primary outcome of

Table 6. Composite Maternal and Neonatal Morbidity

Routine Care (n5101)* Serial 3rd-Trimester USE (n5104) RR (95% CI)

Composite maternal morbidity 9 (9) 9 (9) 1.0 (0.4–2.3)

Chorioamnionitis 4 (4) 5 (5)
Cesarean delivery in labor 6 (6) 5 (5)
Postpartum hemorrhage 3 (3) 2 (2)
Transfusion 3 (3) 1 (1)
Wound infection 0 (0) 1 (1) —
DVT or PE 0 (0) 0 (0) —
Admission to ICU 0 (0) 0 (0) —
Death 0 (0) 0 (0) —
Composite neonatal morbidity 4 (4) 1 (1) 0.2 (0.03–2.1)
Apgar score less than 5 at 5 min 1 (1) 0 (0) —
Umbilical arterial pH less than 7.00† 2 (2) (n592) 0 (0) (n589) —
Intubation longer than 24 h 1 (1) 1 (1)
Periventricular leukomalacia 0 (0) 0 (0) —
IVH grade III or IV 1 (1) 0 (0) —
NEC grade II or III 0 (0) 0 (0) —
Stillbirth 0 (0) 0 (0) —
Neonatal death (within 28 d) 1 (1) 0 (0) —
Birth weight
SGA 8 (8) 8 (8) 1.0 (0.4–2.5)
LGA 7 (7) 3 (3) 0.4 (0.1–1.6)
USE, ultrasound examination; RR, relative risk; DVT, deep venous thrombus; PE, pulmonary embolism; ICU, intensive care unit; IVH,
intraventricular hemorrhage; NEC, necrotizing enterocolitis; SGA, small for gestational age (birth weight less than the 10th percentile for
gestational age using nomogram by Alexander et al); LGA, large for gestational age (birth weight greater than the 90th percentile for
gestational age using nomogram by Alexander et al).
Data are n (%) unless otherwise specified.
* One patient delivered at an outside hospital and the data were not available.
†
Umbilical artery acid base was assessed in 92 (N) cases of routine care and in 89 (N) cases in the serial 3rd-trimester USE.

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Unauthorized reproduction of this article is prohibited.
Table 7. Ultrasound Findings Among Women With Primary Outcomes

Routine Care (n58) Serial 3rd-Trimester USE (n528) P/RR (95% CI)

Initial detection of USE abnormality* (wk of gestation)

Less than 32 0/7 2 (25) 10 (36) .02
32 0/7–34 6/7 2 (25) 8 (29)
35 0/7–36 6/7 3 (38) 0 (0)
37 0/7 or greater 1 (13) 10 (36)
Resolution of abnormal USE findings* 2 (25) 9 (32) 1.3 (0.3–4.8)
Biophysical profile performed for
Abnormalities noted on USE 5 (63) 21 (75) 1.2 (0.7–2.1)
Obstetric complications† 1 (13) 1 (4) .3 (0.02–4.1)
UA Doppler for FGR 2 (25) 8 (29) 1.1 (0.3–4.3)
USE, ultrasound examination; RR, relative risk; UA, umbilical artery; FGR, fetal growth restriction (ultrasound estimated fetal weight less
than the 10th percentile for gestational age).
Data are n (%) unless otherwise specified.
* Sonographic estimate fetal weight less than the 10th percentile or greater than the 90th percentile for gestational age; oligo- or
polyhydramnios.
†
Bleeding, decreased fetal movement, hypertensive disease of pregnancy; preterm labor; premature rupture of membranes, others.

fetal growth abnormalities or oligohydramnios was
similar in both groups, perhaps as a result of the
sample size. Nonetheless, the trend was toward
improved identification of abnormal growth with
serial ultrasound examinations. Previous reports,
however, have described the accuracy of identifying
fetal growth restriction and LGA with ultrasound
examinations.1,2,6,9,22,29,30 This single-center trial was
not powered to detect differences in any obstetric or
neonatal outcomes. Considering the infrequent rate of
morbidity with uncomplicated pregnancies,10,12,13
a large multicenter randomized trial is required to
demonstrate improvement, if any, in outcomes. All
of the ultrasound examinations were done by regis-
tered diagnostic medical ultrasonography-certified ul-
trasonographers; hence, our findings may not be
applicable to women who have third-trimester ultra-
sound examinations by clinicians during prenatal vis-
its.31 The study was done at a tertiary, urban teaching
center, where the population and clinical practice dif-
fer from other locations. We acknowledge that
another limitation of this randomized trial is that the
participants and clinicians were not blinded to group
allocation. This shortcoming, however, permits us
to ascertain the changes in clinical practices
and outcomes if the clinical practice of routine

Table 8. Intrapartum Outcomes

Routine Care (n5101)* Serial 3rd-Trimester USE (n5104) P/RR (95% CI)

Gestational age at delivery (wk)

Less than 37 0/7† 9 (9) 9 (9) .90
37 0/7–38 6/7 31 (31) 35 (34)
39 0/7 or greater 61 (60) 60 (58)
Induction 42 (42) 31 (30) .7 (0.5–1.0)
Induction for ultrasound abnormality alone 6 (6) 15 (14) 2.43 (0.98–6.01)
Delivery route .8 (0.5–1.2)
Vaginal 73 (72) 81 (79)
Cesarean 28 (28) 22 (21)
Cephalopelvic disproportion 2 (7) 3 (14) 1.9 (0.3–10.4)
NR-FHR 9 (32) 5 (23) .7 (0.3–1.8)
Repeat 14 (50) 10 (54) .9 (0.5–1.6)
Other‡ 3 (11) 2 (9) .8 (0.2–4.6)
USE, ultrasound examination; RR, relative risk; NR-FHR, nonreassuring fetal heart rate tracing.
Data are n (%) unless otherwise specified.
* One patient delivered at an outside hospital and the peripartum data were unavailable for analysis.
†
The most common reason for preterm induction was preeclampsia with severe features (4% in routine care and 6% in serial 3rd-trimester
USE).
‡
Other includes cesarean delivery as a result of herpes simplex virus lesion at the time of delivery, malpresentation, inability to abduct as
a result of hip fracture.

VOL. 132, NO. 6, DECEMBER 2018 Ashimi Balogun et al Third-Trimester Ultrasonography vs Routine Care 1365

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third-trimester ultrasound examinations was imple-
mented in uncomplicated pregnancies. Optimally,
the chart abstractor should have been blinded to the
group allocation, but the limited resources and prag-
matic design precluded this option. Nonetheless, it
should be noted that the determination of the primary
and secondary composite outcomes was not deter-
mined by the chart abstractor. Lastly, we did not
undertake a cost-effective analysis to determine
whether the intervention justifies the cost.
The strengths of this randomized trial are notable.
Unlike the prior pilot study,6 we calculated the sample
size to ascertain whether serial ultrasound examina-
tions do improve identification of abnormality of
growth or amniotic fluid. The cohort of women we
recruited was diverse. Our definitions of abnormality
of fetal growth or amniotic fluid were consistent with
the criteria promulgated by ACOG1,21 and reflect cur-
rent clinical practice. The lost to follow-up was less
than 1%. Being a randomized trial in which neither
participants nor clinicians were blinded, our results
provide reasonable estimates of the rate of the com-
posite outcomes of fetal growth restriction, LGA, oli-
gohydramnios, or polyhydramnios in uncomplicated
pregnancies that are managed routinely or with serial
ultrasound examinations in the third trimester.
Our trial should be a nidus for a larger multicen-
ter trial with sufficient power to determine whether
serial ultrasound examinations improve peripartum
outcomes. Previously, investigators suggested that
a trial of 6,000 low-risk pregnancies, randomized to
routine care compared with serial ultrasound exami-
nation, has the power to detect a 36% difference,
assuming the risk of neonatal morbidity is approxi-
mately 4% in the control arm.32 The sample size
would be larger if a different outcome is used10 and
if crossover from one group to another is accounted
for. Such a large trial would permit better assessment
of costs of serial scans (including interventions) in
terms of charges to the patient and resource utiliza-
tion. The larger trial may also demonstrate potential
maternal benefits such as a decreased rate of cesarean
delivery or greater satisfaction.33
In conclusion, among pregnancies without com-
plications at 24 0/7 to 30 6/7 weeks of gestation, serial
third-trimester ultrasound examinations were more
likely to identify abnormalities of fetal growth or of
amniotic fluid than measurements of fundal height.
Before the clinical practice of serial ultrasound exami-
nations is implemented in uncomplicated pregnan-
cies, a larger randomized controlled trial is
warranted.32
1366 Ashimi Balogun et al Third-Trimester Ultrasonography vs Routine Care
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